From Doctor Lloyd Damon, UCSF
Amyloid is a rare disease whereby an abnormal protein deposits in tissues where it does not belong. This harms the tissue. In Irene’s case, the protein is an anti-body called “kappa” which has a propensity to deposit in her kidney. This is causing her to lose normal blood proteins in her urine and is harming her kidney filtering function. Without treatment, kidney failure and short survival is inevitable. The kappa can also build up in the heart, nerves, intestines, liver, etc.
The best treatment for “primary amyloid” is an autologous (self) stem cell transplant (ASCT). This involves collecting bone marrow stem cells out of the blood stream and freezing them (like sperm banking). She would then receive a large dose of a chemotherapy medicine called melphalan. This destroys the antibody producing cells, but also the normal bone marrow.
Two days later we thaw out the frozen stem cells and infuse them like a blood transfusion. These stem cells rebuild the bone marrow and restarts blood production (3 weeks in hospital). The goals for this therapy are to put the amyloid protein production into remission, stabilize or improve the kidney function, and help people live longer. ASCT is not considered a curative treatment for amyloid.
Some Helpful Links
- Nephrotic Syndrome in Adults (American Kidney Fund)
- Amyloidosis (Wikipedia)
- Amyloidosis Support Network
- New insights into systemic amyloidosis: the importance of diagnosis of specific type (Adobe Reader required)
1) Primary Amyloidosis
What is Primary Amyloidosis?
Primary amyloidosis is a disease caused by the abnormal accumulation of protein molecules in body tissues. These proteins are fragments of immunoglobulin (antibody) molecules which are normally present in the blood to give protection against bacteria and other infectious agents. Normally, antibody molecules are constantly being synthesized by cells of the immune system and then, after a finite life span, degraded so that there is a balance between production and degradation.
In this way our active immune system protects our bodies from a constantly changing array of infectious bacteria and viruses. In primary amyloidosis a defect occurs in the immune system. Excessive amounts of certain antibody molecules are produced and fragments of these molecules get deposited in tissues. These tissue deposits, as they enlarge, damage normal tissues and cause the disease that we know as primary amyloidosis.
What causes primary amyloidosis?
The cause of primary amyloidosis is unknown. Since the amyloid protein comes from immunoglobulin molecules, it is possible that some response of the immune system to an infectious bacteria, virus or other foreign substance may trigger the overproduction of antibody protein. So far this is only speculation, because amyloid has not been known to be associated with any particular infection. Indeed, there are no epidemiological data to suggest that amyloid occurs as result of infection. More is known about how the antibody molecules are deposited in tissue and lead to the disease. It is known that antibody molecules are made only by certain cells in the immune system called plasma cells. It is known that plasma cells can synthesize large amounts of antibody molecules but are usually under regulatory mechanisms that maintain a balance.
In primary amyloidosis this balance is disturbed and certain plasma cells synthesize antibody proteins in excess amounts. These proteins, as they circulate through the blood, move out of the blood vessels into tissues where they are polymerized as amyloid deposits. These deposits, which can occur in practically any organ of the body, continue to enlarge until they interfere with normal body functions. If the deposits are in the kidney, they will cause the kidney to have decreased function in getting rid of waste products and eventually the kidneys will fail to meet the body’s needs. If the deposits are in the heart, the heart will have increased difficulty pumping blood and eventually heart failure will occur. If the deposits are in the nerves, a neuropathy will develop with loss of sensation to extremities and motor function to the muscles. Practically all organs in the body can become involved including the stomach and intestines, liver, spleen, skin and lungs. Usually the brain is spared, presumably because there is a “blood brain barrier” which restricts the movement of antibody molecules into the central nervous system.
Who gets primary amyloidosis?
Primary amyloidosis is an uncommon disease but because it causes symptoms which are similar to many other diseases (for example, nephritis, atherosclerotic heart disease, cancer and gastrointestinal disease), the diagnosis is frequently missed and the true incidence cannot be determined. Primary amyloidosis affects both men and women and has been reported to occur in individuals from the 20’s to the later decades of life. The peak occurrence is around age 60-65 but many patients get the disease in their 40’s and 50’s.
What happens in primary amyloidosis?
Although amyloid proteins can deposit in any organ that has unrestricted blood supply, accumulations of amyloid protein in certain organs will cause illness much faster than others. For example, large amounts of amyloid can be present in the spleen without giving significant symptoms. It is well known that the spleen can be surgically removed and the body can function without problems. Small deposits of amyloid in the heart, however, can cause disruption of the electrical system that makes the heart beat and can be extremely life threatening. The most common organs to suffer from amyloid deposits are the kidney, heart, and liver.
The diagnosis of primary amyloidosis can only be firmly established by tissue biopsy. By sampling a small amount of tissue from an affected organ, the amyloid deposits can be demonstrated with special stains on microscopic sections of the tissue. Of course, a tissue biopsy of the organ involved with amyloid deposits would give the greatest chance of making the definite diagnosis, but often biopsy of affected organs is not easy to accomplish without risk. For instance, there is a certain amount of risk to having a heart biopsy, although biopsy using a catheter as is used for cardiac catheterization studies makes this more easily done. Biopsies of liver or kidney can result in bleeding which is an unwanted and potentially life threatening complication. For these reasons, biopsies of rectal mucosa through a sigmoidoscope or a biopsy of the skin are often used as the first test in confirming the diagnosis of amyloidosis. If the rectal mucosa or skin biopsy is positive for amyloidosis, then the doctor can assume that abnormalities affecting internal organs are due to the amyloidosis. Certain other tests are used to diagnose amyloidosis and, while suggestive of this condition, are not definitive. A large majority of patients with primary amyloidosis have evidence of abnormal antibody molecules in the blood stream and these can be demonstrated by certain tests. Echocardiograms, electrocardiograms, x-ray studies can suggest the diagnosis of amyloidosis and can be helpful in evaluating the patient.
Primary amyloidosis is usually a progressive disease which in the majority of patients leads to death from kidney or heart failure. There are not good data on how long a patient may have amyloidosis before it reaches the point where sickness from organ dysfunction commences, but there are fairly good data that show that the life expectancy after diagnosis is in the range of 1 to 1-1/2 years. Of course there are persons who live several years with primary amyloidosis and there are patients who succumb to the disease within a few weeks after the diagnosis is made. Most of these latter patients have, in retrospect, been ill for some time but the diagnosis was not made either because the patient did not seek medical help or the symptom complex was not typical for amyloidosis and the diagnosis not made.
There is no specific treatment for primary amyloidosis that has been proven to be effective and results in prolonged survival. A number of treatment modalities including special diets, vitamins, DMSO have been tried without any positive results. In some patients, treatment with high doses intravenous melphalan followed by bone marrow stem cell rescue (autologous bone marrow transplant) has proven effective. This therapy however is not indicated for patients with severe heart amyloidosis or extensive disease in other organs. The most common treatment for primary amyloidosis that is used by physicians includes chemotherapy consisting of Alkeran (Melphalan) and Prednisone. These drugs have been shown to be effective in the treatment of multiple myeloma which is also a disorder of the immune system but which is generally considered to be a malignant disease. Some studies have suggested that chronic treatment with Colchicine, which has been used for many years for the treatment of gout, may slow down the progress of primary amyloidosis.
While there is not specific treatment for primary amyloidosis, many of the manifestations of amyloidosis can be treated effectively. These include the use of diuretics to correct the abnormalities of kidney and heart failure. Antibodies may be of help in treating the gastrointestinal manifestations of amyloidosis. Kidney dialysis has been used for patients whose kidney function has been reduced below the levels needed to sustain life.
Medical research is being done to find the cause and prevention of primary amyloidosis. These studies are aimed at defining the mechanisms that are disrupted so that the immune system is not in balance. Other studies are aimed at determining how fragments of antibody molecules are polymerized to make amyloid deposits. With knowledge about these mechanisms of amyloid formation, it is hoped that specific therapies for treating primary amyloidosis can be devised and that the deposition of amyloid material in tissues can be halted. In addition to these basic forms of research, newer therapies are being tried to see if the progression of amyloid formation can be altered.